The presence of the pentafluorosulfanyl (SF5) group imparts a number of favorable physical and chemical characteristics including thermal, hydrolytic, and chemical stability, high density, high electronegativity, and high lipophilicity. These favorable characteristics have prompted a high degree of interest in SF5-organics for potential applications in the biomedical and materials fields (Altomonte & Zanda, J. Fluorine Chem. 2012, 143, 57-93). As such, pentafluorosulfanyl-substituted compounds are undergoing extensive studies for use as high performance polymers, liquid crystals, pharmaceuticals and pesticides (Thayer, Chem. Eng. News 2006, 84:27-32).
As a substituent on an aromatic ring the SF5 group acts as a sterically demanding, strongly electron-withdrawing/deactivating group. A major drawback in the development of synthetic chemistry of SF5-arenes has been the lack of practical methods that avoid the use of exotic/hazardous reagents and harsh conditions. In early pioneering studies Sheppard synthesized the parent (pentafluorosulfanyl)benzene and its p-nitro derivative in modest yields by reacting the corresponding aryl disulfides or aryl sulfur trifluorides with excess AgF2 in chlorofluorocarbon solvent at elevated temperatures in a copper reactor (Sheppard, J. Am. Chem. Soc. 1962, 84, 3064-3072). This method was later employed by Thrasher et al. (Sipyagin, et al., J. Fluorine Chem. 2001, 112, 287-295; Sipyagin, et al., J. Fluorine Chem. 2004, 125, 1305-1316) to prepare various substituted derivatives of PhSF5 in modest overall yields and many side products. Subsequent methods reported from other laboratories involved elemental fluorination starting with the corresponding bisnitrophenyl disulfide, (Bowden, et al., Tetrahedron 2000, 56, 3393-3408; Kirsch & Hahn, Eur. J. Org. Chem. 2005, 3095-3100; Kirsch & Hahn, Eur. J. Org. Chem. 2006, 1125-1131; Kirsch, et al., Angew. Chem. 1999, 111, 2174; Kirsch, et al., Angew. Chem. Int. Ed. 1999, 38, 1989-1992) and high pressure reactions with gaseous SF5 halides (Sergeeva & Dolbier Jr, Org. Lett. 2004, 6, 2417-2419; Winter & Gard, J. Fluorine Chem. 2004, 125, 549-552). The 3-nitro derivative is accessible by direct electrophilic nitration of PhSF5 (Sheppard, J. Am. Chem. Soc. 1962, 84, 3064-3072; Bowden, et al., Tetrahedron 2000, 56, 3393-3408; Kirsch & Hahn, Eur. J. Org. Chem. 2005, 3095-3100; Kirsch & Hahn, Eur. J. Org. Chem. 2006, 1125-1131; Kirsch, et al., Angew. Chem. 1999, 111, 2174; Kirsch, et al., Angew. Chem. Int. Ed. 1999, 38, 1989-1992; Sergeeva & Dolbier Jr, Org. Lett. 2004, 6, 2417-2419). A recent method reported by Umemoto et al. (Umemoto, et al., Beilstein J. Org. Chem. 2012, 8, 461-471) involves synthesis of ArSF4Cl from ArSSAr or ArSH by reaction with Cl2/KF or CsF and subsequent transformation to ArSF5 by ZnF2/heat.
The strongly deactivating effect of SF5 group makes PhSF5 amenable to SNAr chemistry notably with alkoxides and thiolate, (Beier, et al., Org. Lett. 2011, 13, 1466-1469) and by vicarious nucleophilic substitution of hydrogen (Beier, et al., J. Org. Chem. 2011, 76, 4781-4786; Iakobson, et al., Synlett 2013, 24, 855-859; Vida & Beier, J. Fluorine Chem. 2012, 143, 130-134). By contrast, the SEAr chemistry of SF5-aromatics has remained under-developed. In early work by Bowden (Bowden, et al., Tetrahedron 2000, 56, 3393-3408) the 3-iodo and 4-iodo derivatives were synthesized by in-situ diazotization and reaction with KI, and were shown to enter into cross coupling reactions in representative cases. Formation of an SF5-based azo-dye by in-situ diazotization and coupling to PhNMe2 was reported by Kirsch and Hahn (Kirsch & Hahn, Eur. J. Org. Chem. 2006, 1125-1131). However, the F5S—C6H4N2+ salt was never isolated in earlier studies to allow its use as a key building block for the synthesis of other SF5-aromatics using diazonium ion chemistry.
The commercial availability of parent PhSF5 and a few other derivatives, notably the p-Me, the p-NH2, and the m- and p-NO2 derivatives has remedied some of the preparatory problems. However, there are only a few readily available pentafluorosulfanyl compounds, significantly limiting the use of pentafluorosulfanyl-based synthesis. Much of the current technology focuses on synthetic methods that use of exotic and/or hazardous reagents and harsh conditions. As such, what is required is a readily available starting pentafluorosulfanyl-substituted compound for use in pentafluorosulfanyl-based synthesis.